Table 1.
Genes located in the 1.5Mb Critical Region of 22q11.2DS
| Gene Symbol |
Name | Function (/Hypothesized Function) | Expression in HPC or forebrain? |
Abnormal brain-related phenotypes of knockout mice |
|---|---|---|---|---|
| DGCR6 | diGeorge Syndrome Critical Region Gene 6 | Unknown function. Protein has homology with D. melanogaster gonadal protein and the gamma-1 subunit of human laminin. | Yes | |
| PRODH | Proline Dehydrogenase (Oxidase) 1 | Mitochondrial enzyme proline dehydrogenase that catalyzes the first step in the degradation of L-proline, a putative neuromodulator. Defects in this gene cause hyperprolinemia type 1. | Yes | Prodh-deficient mice: Altered synaptic transmission, reduced PPI, impaired fear conditioning, altered cortical dopaminergic transmission. |
| DGCR5 | diGeorge Syndrome Critical Region Gene 5 (non-coding) | N/A | ||
| DGCR9 | diGeorge Syndrome Critical Region Gene 9 | Unknown. | ||
| DGCR1 | diGeorge Syndrome Critical Region Gene 1 | Unknown | ||
| DGCR2 | kiaa163 Gene Product | Predicted novel adhesion receptor protein. | Yes | |
| DGCR11 | diGeorge Syndrome Critical Region Gene 11 | Unknown. | ||
| DGCR14 | diGeorge Syndrome Critical Region Gene 14 | Protein may be a component of spliceosomes. Mouse orthologue has nuclear localization. | Yes | |
| TSSK2 | Testis-Specific Serine Kinase 2 | Member of a family of serine/threonine kinases; highly expressed in testis | Yes | |
| GSC2 | Goosecoid-like | A homeodomain-containing gene, expressed in a limited number of adult tissues and in early development. | Yes | |
| SLC25A1 | Solute Carrier Family 25, Member 1 | Mitochondrial carrier, citrate transporter. | Yes | |
| CLTCL1 | Clathrin, Heavy Polypeptide-like 1 | A major protein of the polyhedral coat of coated pits and vesicles. NB. Not present in mouse syntenic region. | ||
| HIRA | Hir Histone Cell Cycle Regulation Defective Homolog A (S. cerevisiae) | A histone chaperone that preferentially places the variant histone H3.3 in nucleosomes. May play an important role in the formation of transcriptionally silent heterochomatin. | Yes | Knockout: Embryonic lethal; abnormal morphology of head, forebrain, neural tube, embryonic neuroepithelium, neural plate and altered hindbrain development. |
| MRPL4 | Nuclear Localization Signal Deleted in Velocardiofacial Syndrome | A mammalian mitochondrial ribosomal protein; controls protein synthesis in mitochondria. | Yes | |
| C22orf39 | Hypothetical Protein loc128977 | Unknown. | ||
| UFD1L | Ubiquitin Fusion Degradation 1-like (S. cerevisiae) | Protein necessary for the degradation of ubiquitinated proteins. Regulates the disassembly of the mitotic spindle and the formation of a closed nuclear envelope after mitosis. | Yes | |
| CDC45L | cdc45 Cell Division Cycle 45-like (S. cerevisiae) | Highly homologous to the S. cerevisiae Cdc45, a protein required to the initiation of DNA replication. | Yes | |
| CLDN5 | Claudin 5 (Transmembrane Protein Deleted in Velocardiofacial Syndrome) | A major cell adhesion molecule of tight junctions in brain endothelial cells. | Yes | Knockout: Neonatally lethal; blood-brain barrier against small molecules (<8 D) was selectively affected. |
| LOC15185 | Unknown. | |||
| SEPT5 | Septin 5 | Member of the septin gene family; regulation of cytoskeleton. | Yes | Knockout + Heterozygote: Decreased anxiety-related response, Abnormal spatial learning. Knockout: Abnormal social/conspecific interaction, increased PPI. |
| GP1BB | Glycoprotein ib (platelet), Beta Polypeptide | A heterodimeric transmembrane protein that constitutes the receptor for von Willebrand factor, and mediates platelet adhesion. Mutations in the gene have been associated with Bernard-Soulier syndrome and giant platelet disorder. | Yes | |
| TBX1 | t-box 1 | Member of a family of transcription factors that share a common DNA-binding domain, the T-box. Responsible for many physical symptoms of 22q11.2 DS. | Yes | Heterozygote: Decreased PPI |
| GNB1L | Guanine Nucleotide Binding Protein (G- Protein), Beta Polypeptide 1-like | Encodes a G-protein beta-subunit-like polypeptide containing WD repeats. | Yes | Heterozygote: Decreased PPI. |
| C22orf29 | Hypothetical Protein flj21125 | Unknown. | ||
| TXNRD2 | Thioredoxin Reductase 2 | Member of a family of pyridine nucleotide-disulfide oxidoreductases; regulation of the intracellular redox environment. | Yes | |
| COMT | Catechol-o-Methyltransferase | Catalyzes the transfer of a methyl group from S-adenosylmethionine to catecholamines. One of the major degradative pathways of the catecholamine transmitters. | Yes | Heterozygote: Reduced clearance of cortical dopamine, increased aggression towards males, altered anxiety-related response, cognitive deficits. |
| ARVCF | Armadillo Repeat Gene Deletes in Velocardiofacial Syndrome | A member of the catenin family; encodes a protein containing a coiled coil domain and an armadillo repeat sequence as well as a predicted nuclear-targeting sequence. | Yes | |
| C22orf25 | Chromosome 22 Open Reading Frame 25 | Unknown | Yes | |
| DGCR8 | diGeorge Syndrome Critical Region Gene 8 | Encodes for a component of the “microprocessor”, a nuclear complex involved in microRNA processing. | Yes | Knockout is embryonic lethality before somite formation. Heterozygote: Abnormal dendrite morphology, abnormal spatial working memory, decreased prepulse inhibition. |
| TRMT2A | Yes | |||
| RANBP1 | Ran Binding Protein 1 | Protein binds to RAN complexed with GTP but not GDP and markedly increases GTP hydrolysis by the RanGTPase-activating protein. | Yes | |
| ZDHHC8 | Zinc Finger, DHHC-type Containing 8 | Member of the DHHC family of palmitoyl-transferases | Yes | Female knockout and heterozygote: decreased exploration in new environment, reduced PPI. Knockout and heterozygote: Abnormal dendrite and spine morphology. |
| LOC15197 | Unknown. | |||
| RTN4R | Reticulon 4 Receptor / Nogo receptor 1 | Receptor for reticulon 4 (Nogo receptor 1); mediation of axonal growth inhibition and may play a role in regulating axonal plasticity in the adult CNS. | Yes | Heterozygote: Hypoactivity, impaired coordination, decreased exploration in new environment, abnormal central nervous system regeneration, axon outgrowth and plasticity. |
| DGCR6L | diGeorge Syndrome Critical Region Gene 6-like | One of two functional genes encoding nearly identical proteins that have similar expression patterns. NB. Not present in mouse syntenic region. |
Genes listed according to the RefSeq genes (DGCR6-DGCR6L). Evidence for expression patterns was taken from http://www.informatics.jax.org/expression.shtml. Where phenotypic data is available for heterozygous knockout animals it is given, where it is of interest data from knockout studies are summarized.